Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study
Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study
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DOI：
10.1016/s2352-3018(15)00211-8
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发表时间：
2016-01-01
期刊：
影响因子：
16.1
通讯作者：
Ryom, Lene
中科院分区：
文献类型：
--
作者：
Mocroft, Amanda;Lundgren, Jens D.;Ryom, Lene
背景用于治疗HIV感染的抗逆转录病毒药物与慢性肾脏疾病之间是否存在累积关系是一个有争议的话题，特别是在最初肾功能正常的患者中。在这项研究中，我们的目的是调查接触抗逆转录病毒药物的持续时间与最初肾功能正常的人发生慢性肾脏疾病之间的关系，通过估计肾小球滤过率（eGFR）进行测量。（年龄>= 16岁）从D：A：d研究（总部位于欧洲、美国、与基线相比，对首次eGFR> 90 mL/min/1.73 m2的患者进行随访（2004年1月1日之后的首次eGFR测量），直至发生以下情况之一：慢性肾脏疾病;末次eGFR测量; 2014年2月1日;或末次访视加6个月（以先发生者为准）。慢性肾脏疾病定义为经证实（间隔> 3个月）eGFR低于60 mL/min/1.73 m2。主要结局是慢性肾脏疾病的发生。Poisson回归用于估计与富马酸替诺福韦酯、利托那韦增强的阿扎那韦、利托那韦增强的洛匹那韦、其他利托那韦增强的蛋白酶抑制剂或阿巴卡韦的累积暴露相关的慢性肾脏疾病的发病率。受试者的基线eGFR中位数为110 mL/min/1.73 m2（IQR 100 - 125），中位年龄为39岁（33 - 45），中位CD4细胞计数为441个细胞/mm3（294 - 628）。在中位随访7.2年（IQR 5.1 - 8.9）期间，23905人中有285人（1%）发展为慢性肾脏疾病（发病率为1.76/1000人-年[95% CI 1.56 - 1.97]）。调整后，我们记录到富马酸替诺福韦酯暴露每增加一年，慢性肾脏疾病的发病率显著增加（调整后的发病率比为1.14 [95%CI 1.10 - 1.19]，p
Background Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR).Methods In this prospective international cohort study, HIV-positive adult participants (aged >= 16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1.73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1.73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir- boosted atazanavir, ritonavir- boosted lopinavir, other ritonavir- boosted protease inhibitors, or abacavir.Findings Between Jan 1, 2004, and July 26, 2013, 23 905 eligible individuals from the D: A: D study were included. Participants had a median baseline eGFR of 110 mL/min per 1.73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7.2 years (IQR 5.1-8.9), 285 (1%) of 23905 people developed chronic kidney disease (incidence 1.76 per 1000 person-years of follow-up [95% CI 1.56-1.97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1.14 [95% CI 1.10-1.19], p